Topical Hydroquinone Research Articles

Melasma treated with hydroquinone, tretinoin, and a fluorinated steroid.

A retrospective study was conducted in six Hispanic women, 35–55 years of age, with Fitzpatrick skin types IV to VI, presenting to an academic dermatology clinic for resistant melasma (Table 1). They had all been treated with topical hydroquinone (2–4%) without success prior to being seen in our clinic. Patient demographics Patient Age Country of origin Affected area Duration of disease (years) Severity Type of melasma 1 39 El Salvador Cheeks, upper lip 10 Moderate Epidermal 2 37 Mexico Cheeks 12 Moderate Epidermal 3 35 Mexico Cheeks 7 Moderate Combination 4 35 Mexico Cheeks 9 Moderate Epidermal 5 55 Mexico Cheeks, jaw 20 Moderate Combination 6 32 Mexico Cheeks, forehead 6 Moderate Epidermal A Wood's lamp was used to determine whether the melasma was epidermal, dermal, or a combination of the two. The patients were treated with a mixture containing 0.05% tretinoin cream, 0.05% triamcinolone acetonide cream, 6% hydroquinone, and 0.1% ascorbic acid (as a preservative) applied at night, and a sun protection factor (SPF) 15 UVB‐blocking sunscreen was applied each morning. They were instructed to use the mixture on the affected areas nightly for a period of 8 weeks. All of the patients were evaluated at baseline and monthly during the treatment period. Improvement in pigmentation was assessed at each subsequent visit by clinical examination and photography with polarized filters as well as black and white UV reflectance photography (Canfield Scientific, Inc.). Improvement was determined subjectively on a three‐point scale as follows: I, mild improvement; II, moderate improvement; III, significant improvement.

Management of facial hyperpigmentation.

Facial and neck pigmentations are the most cosmetically important. They are common in middle-aged women, and are related to endogenous (hormones) and exogenous factors (such as use of cosmetics and perfumes, and exposure to sun radiation). Melasma (chloasma) is the most common cause of facial pigmentation, but there are many other forms such as Riehl's melanosis, poikiloderma of Civatte, erythrose peribuccale pigmentaire of Brocq, erythromelanosis follicularis of the face and neck, linea fusca, and cosmetic hyperpigmentations. Treatment of melasma and other facial pigmentations has always been challenging and discouraging. It is important to avoid exposure to the sun or to ultraviolet lamps, and to use broad-spectrum sunscreens. Several hypopigmenting agents have been used with differing results. Topical hydroquinone 2 to 4% alone or in combination with tretinoin 0.05 to 0.1% is an established treatment. Topical azelaic acid 15 to 20% can be as efficacious as hydroquinone, but is less of an irritant. Tretinoin is especially useful in treating hyperpigmentation of photoaged skin. Kojic acid, alone or in combination with glycolic acid or hydroquinone, has shown good results, due to its inhibitory action on tyrosinase. Chemical peels are useful to treat melasma: trichloroacetic acid, Jessner's solution, Unna's paste, alpha-hydroxy acid preparations, kojic acid, and salicyclic acid, alone or in various combinations have shown good results. In contrast, laser therapies have not produced completely satisfactory results, because they can induce hyperpigmentation and recurrences can occur. New laser approaches could be successful at clearing facial hyperpigmentation in the future.

HUMAN IN VIVO AND IN VITRO HYDROQUINONE TOPICAL BIOAVAILABILITY, METABOLISM, AND DISPOSITION

Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3 +/- 11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 mug/cm 2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC) . Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same R as benzoquinone, which was decreased with azide f treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.

Topical hydroquinone in the treatment of some hyperpigmentary disorders

Seventy patients (50 with melasma, 10 with freckles, and 10 with post‐inflammatory hyperpigmentation) were admitted to this trial. Treatment in the form of 4% hydroquinone (HQ) was applied topically twice daily for a maximum of 12 weeks. Patients were advised to avoid sun exposure and/or to use topical sunscreen during the entire period of treatment.All patients were examined at week 0 and at weeks 4, 8, and 12 of therapy. At each visit, the lesion size was determined and the pigmentary intensity of melasma, freckles, and the area of post‐inflammatory hyperpigmentation (PIH) relative to a non‐affected area of skin was rated on a four‐point scale: 1, no difference; 2, mild pigmentation; 3, moderate pigmentation; 4, severe pigmentation. At the last visit, the overall response was rated as excellent, good, fair, or poor.

Tretinoin Clears Postinflammatory Hyperpigmentation in Black Persons

Although topical tretinoin (retinoic acid) has been used since the mid 1970s in combination with mild topical corticosteroids and hydroquinone in the

'Fade out'photochromonychia

Two English women are described who developed chestnut-brown pigmentation of the distal part of the finger- and thumb-nail plates whilst using 'over the counter' topical hydroquinone depigmenting creams. In both individuals there was marked deepening of the pigmentation during periods of intense sun exposure. Withdrawal or protection of the nails from the hydroquinone resulted in resolution of the pigmentation. Hydroquinone staining of the nails is not well recognized and this report confirms a previous suggestion of a relationship between the intensity of the pigmentation and light exposure.

Azelaic Acid

Azelaic acid is a naturally occurring saturated dicarboxylic acid which, on topical application (usually as a 20% cream), has been shown to be effective in the treatment of comedonal acne and inflammatory (papulopustular, nodular and nodulocystic) acne, as well as various cutaneous hyperpigmentary disorders characterised by hyperactive/abnormal melanocyte function, including melasma and, possibly, lentigo maligna. In addition, azelaic acid has an antiproliferative and cytotoxic effect on the human malignant melanocyte, and preliminary findings indicate that it may arrest the progression of cutaneous malignant melanoma. The mechanism of this selective cytotoxic action of azelaic acid is unclear, but may possibly be related to its inhibition of mitochondrial oxidoreductase activity and DNA synthesis. In controlled studies, topical azelaic acid demonstrated comparable anti-acne efficacy to topical tretinoin, benzoyl peroxide, erythromycin and oral tetracycline, while in patients with melasma azelaic acid proved at least as effective as topical hydroquinone. On topical application azelaic acid is well tolerated, with adverse effects apparently limited to a generally mild and transient local cutaneous irritation. Thus, topical azelaic acid, employed either as monotherapy or in combination with other treatments, is likely to prove of value in the management of acne and several hyperpigmentary disorders, most notably melasma.

Exogenous ochronosis superimposed on chronic kidney disease: A case report and review of literature

Ochronosis is a rare disease characterized by speckled and diffuse pigmentation symmetrically over the face, neck, and photo-exposed areas. It can present in exogenous or endogenous form. Endogenous ochronosis or alkaptonuria is an autosomal recessive disease caused by a deficiency of homogentisic acid (HGA) oxidase, which results in the accumulation of HGA, a hydroquinone (HQ) metabolite of tyrosine. Some evidence suggests that it is not HGA itself but a by-product of its oxidation, a benzoquinone acetic acid, that can polymerize to a melanin-like pigment by unknown mechanisms and accumulates both inter and intracellularly in connective tissue, most commonly the joints, cardiovascular system, kidney, skin, and glands, a pathological condition known as ochronosis (Development of an in vitro model to investigate joint ochronosis in alkaptonuria. Tinti L, Taylor AM et al. Rheumatology 2010; Oct 15: 1-7. doi: 10.1093/rheumatology/keq246). Exogenous ochronosis (EO) is a rare, cosmetically disfiguring condition, resulting from the long-term use of topical HQ in the treatment of melasma. It manifests as grey-brown or blue-black macules in HQ-exposed regions, characterized histologically by banana-shaped ocher-colored deposits in the dermis. HQ the topical bleaching agent of choice is widely prescribed by physicians and often used by patients without a prescription. The principal adverse effects of its chronic use are confetti-like depigmentation and rarely EO. EO is an avoidable dermatosis that needs to be recognized early with immediate discontinuation of HQ as treatment is difficult. Sun exposure facilitates the formation of EO and must be strictly avoided. We report case of a 65-year-old man who had chronic kidney disease but developed EO while using topical HQ.

Topical Use of Hydroquinone for Depigmentation

Autoxidation of hydroquinone in ointments used for depigmentation may reduce its effectiveness. In this study low concentrations (2%, 3%, 5%) of stabilized hydroquinone were used for depigmenting old age spots on the hands of 94 white men. Also treated were 43 Negro men with normal skin. Higher concentrations of hydroquinone may produce sensitization. Lower concentrations are less likely to. Although the depigmentation produced by topical hydroquinone is limited, it is, in our experience, the best available depigmenting agent.